title: Discriminant analysis of prion sequences for prediction of susceptibility.
abstract: Prion diseases, including ovine scrapie, bovine spongiform encephalopathy (BSE), human kuru and Creutzfeldt-Jakob disease (CJD), originate from a conformational change of the normal cellular prion protein (PrP(C)) into abnormal protease-resistant prion protein (PrP(Sc)). There is concern regarding these prion diseases because of the possibility of their zoonotic infections across species. Mutations and polymorphisms of prion sequences may influence prion-disease susceptibility through the modified expression and conformation of proteins. Rapid determination of susceptibility based on prion-sequence polymorphism information without complex structural and molecular biological analyses may be possible. Information regarding the effects of mutations and polymorphisms on prion-disease susceptibility was collected based on previous studies to classify the susceptibilities of sequences, whereas the BLOSUM62 scoring matrix and the position-specific scoring matrix were utilised to determine the distance of target sequences. The k-nearest neighbour analysis was validated with cross-validation methods. The results indicated that the number of polymorphisms did not influence prion-disease susceptibility, and three and four k-objects showed the best accuracy in identifying the susceptible group. Although sequences with negative polymorphisms showed relatively high accuracy for determination, polymorphisms may still not be an appropriate factor for estimating variation in susceptibility. Discriminant analysis of prion sequences with scoring matrices was attempted as a possible means of determining susceptibility to prion diseases. Further research is required to improve the utility of this method.
authors.affiliation: 1] Laboratory of Computational Biology and Bioinformatics, Graduate School of Public Health, Seoul National University, Gwanak-gu, Korea [2] Interdisciplinary Graduate Program in Bioinformatics, College of Natural Science, Seoul National University, Gwanak-gu, Korea.
authors.forename: Ji-Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Se-Eun
authors.initials: SE
authors.lastname: Bae
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Jung
authors.forename: Insung
authors.initials: I
authors.lastname: Ahn
authors.forename: Hyeon Seok
authors.initials: HS
authors.lastname: Son
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016002:Discriminant Analysis; D004198:Disease Susceptibility; D006801:Humans; D008322:Mammals / Q000235:genetics; D009154:Mutation; D011110:Polymorphism, Genetic; D017096:Prion Diseases / Q000235:genetics; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA
chemical_list: D011328:Prions